Нові оксазоліни з сульфолановим фрагментом

Oxazolines are widely used as synthons for medicines and their production, as protection for structural fragments of reaction centers, as well as ligands. We for the first time examined the ability of cis- and trans-3-hydroxy-4-aminosulfolanov to form oxazolines. Oxazolines are formed by cyclization of the corresponding N-acyl derivatives of trans-3-hydroxy-4-aminosulfolan under reflux in thionyl chloride; amides of cis-isomer aminoalcohol under the same conditions of the reaction do not formed identically product. These results confirm that the oxazoline cycle formed by realization of intramolecular SN2- mechanism using thionyl chloride as dehydrating agent; alternative mechanism (the attack of the hydroxyl group on carbon of amide group) can not be realized using the microwave radiation reaction mass.Оксазолины широко используются в качестве лекарств и синтонов для их получения, структурных фрагментов для защиты реакционных центров, а также лигандов в асимметрических синтезах. Нами впервые исследована способность изомерных цис- и транс-3-гидрокси-4-аминосульфоланов к образованию оксазолинов. Оксазолины синтезированы циклизацией соответствующих N-ацильных производныхтранс-3-гидрокси-4-аминосульфолана при кипячении в хлористом тиониле; амиды цис-изомерного аминоспирта в тех же условиях проведения реакции продукта не образуют. Полученные результаты подтверждают, что оксазолиновый цикл образуется путем реализации внутримолекулярного SN2-подобного механизма при использовании хлористого тионила в качестве дегидратирующего реагента.Оксазоліни широко використовуються у якості ліків та синтонів для їх отримання; як  структурні фрагменти для захисту реакційних центрів, а також у якості лігандів. Нами вперше досліджено здатність ізомернихцис- та транс-3-гідрокси-4-аміносульфоланів до утворення оксазолінів. Оксазоліни утворюються шляхом циклізації відповідних N-ацильних похідних транс-3-гідрокси-4-аміносульфолану при кип’ятінні у хлористому тіонілі; аміди цис-ізомерного аміноалкоголю за тих же умов проведення реакції не утворюють тотожного продукту. Отримані результати підтверджують, що оксазоліновий цикл утворюється через реалізацію внутрішньомолекулярного SN 2-подібного механізму за умов використання хлористого тіонілу у якості дегідруючого реагенту; альтернативний механізм (атака гідроксильної групи по карбону амідної групи) не реалізується при застосуванні мікрохвильового опромінення реакційної маси

New oxazilines with sulfolane frame

Oxazolines are widely used as synthons for medicines and their production, as protection for structural fragments of reaction centers, as well as ligands. We for the first time examined the ability of cis- and trans-3-hydroxy-4-aminosulfolanov to form oxazolines. Oxazolines are formed by cyclization of the corresponding N-acyl derivatives of trans-3-hydroxy-4-aminosulfolan under reflux in thionyl chloride; amides of cis-isomer aminoalcohol under the same conditions of the reaction do not formed identically product. These results confirm that the oxazoline cycle formed by realization of intramolecular SN2- mechanism using thionyl chloride as dehydrating agent; alternative mechanism (the attack of the hydroxyl group on carbon of amide group) can not be realized using the microwave radiation reaction mass

General and Scalable Approach to Trifluoromethyl-substituted Cyclopropanes

CF3-cyclopropanes were prepared on a multigram scale by deoxyfluorination of cyclopropane carboxylic acids or their salts with sulfur tetrafluoride. For labile α-pyridine acetic acids, only the use of salts allowed to obtain the needed products. Derivatization of CF3-cyclopropanes into building blocks ready for the direct use in medicinal chemistry was performed

1,2-Disubstituted Bicyclo[2.1.1]hexanes as Bioisosteres of the ortho-substituted Benzene

1,2-Disubstitued bicyclo[2.1.1]hexanes have been designed, synthesized, and validated as a new generation of saturated bioisosteres of ortho-substituted benzenes. Incorporation of the bicyclo[2.1.1]hexane core into the structure of agrochemicals Boskalid (BASF), Bixafen (Bayer CS), and Fluxapyroxad (BASF) gave saturated analogs that exhibited a high antifungal activity

Unexpected Discovery of Saturated Pyridine Mimetics

A general approach to 3-azabicyclo[3.1.1]heptanes was unexpectedly discovered. The mechanism, scope, and scalability of this method were studied. The core was incorporated into the structure of the antihistamine drug Rupatidine instead of the pyridine ring, which led to a dramatic improvement in physicochemical properties

An “Ideal” Bioisoster of the para-substituted Phenyl Ring

The phenyl ring is a basic structural element in chemistry, and we learn about it already in school. We have developed an “ideal” saturated bioisoster of the para-substituted phenyl ring, - 2 oxabicyclo[2.2.2]octane. Its incorporation into Imatinib drug led to dramatic improvement of all physicochemical properties. This study opens new horizons in science, given the commonplace of the phenyl ring everywhere

The LARGEST library of Bicyclo[1.1.1]pentanes for Drug Discovery enabled by Light

In 2012, bicyclo[1.1.1]pentanes were demonstrated to be bioisosteres of the phenyl ring. Today, after more than a decade, the difficulty in their large-scale preparation is still a problem, that often outweighs the corresponding derivatives to becoming clinical candidates. Here, we report a practical general reaction that gives bicyclo[1.1.1]pentanes on mg- to kg-quantities using just light. No additional additives or catalysts are needed. Using this strategy, we have prepared >300 functionalized bicyclo[1.1.1]pentanes on a (multi)gram scale. So far, this is the most general and practical approach to bicyclo[1.1.1]pentanes. Many of these molecules, which were previously commercialized, are already being used in drug discovery by pharmaceutical companies Gilead Sciences, Hoffman-La Roche, Idorsia, Merck, Janssen Pharm., etc. This work should ease the transition of bicyclo[1.1.1]pentane-containing bioactive compounds to clinical candidates, and subsequently to drugs

Fluorinated Aliphatic Diazirines: Preparation, Characterization, and Model Photolabeling Studies

The previously unknown difluoromethyl diazirines and the previously neglected trifluoromethyl-aliphatic diazirines were synthesized and characterized. Model photolabeling experiments and biological studies showed that these compounds could indeed be used as photoaffinity labels

Fluorinated Aliphatic Diazirines: Preparation, Characterization, and Model Photolabeling Studies

The previously unknown difluoromethyl diazirines and the previously neglected trifluoromethyl-aliphatic diazirines were synthesized and characterized. Model photolabeling experiments and biological studies showed that these compounds could indeed be used as photoaffinity labels